Osteoarthritis (OA) is the most common musculoskeletal disease and it affects about 10% of the world's population aged 60 and older. Buckwalter, J. A. and Martin, J. A. Adv. Drug Deliv. Rev., 58, 150 (2006). OA affects the entire joint and is characterized by a loss of cartilage. Conventional OA treatment consists of nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesics. Reviewed in, e.g., Reginster, J-Y., et al. Mini-Reviews in Medicinal Chemistry, 7, 1051-1061 (2007). However, many of these drugs can cause serious side effects and therefore strategies have been developed for using chondroitin sulfate as a means for treating OA. Chondroitin sulfate (CS) is widely used to treat OA. See, e.g., Reginster et al., “Symptom and Structure Modifying Properties of Chondroitin Sulfate in Osteoarthritis,” Mini-Reviews in Med. Chem., 7: 1051-61 (2007). CS is classified as a symptomatic slow acting drug in osteoarthritis (SYSADOAs), acting after a few weeks time, as compared to analgesics and NSAIDs, which act within a few hours.
Chondroitin sulfate (CS) is a major component of the extracellular matrix, and is found in animal cartilage. CS is a sulfated glycosaminoglycan (GAG) consisting of repeating units of alternating glucuronic acid and N-acetyl-galactosamine that contains sulfate groups at one or more positions on the N-acetyl-galactosamine units, such as the 4 position (CS A), 6 position (CS C), 2 position (CS D) or the 4 and 6 positions (CS E). While the size of CS varies, typical CS molecules have a size of about 20,000 to 50,000 daltons. Current sources of CS include cartilage from various animals, such as pigs (ear and nose), cows (trachea), sharks, fish and birds.